Gestational and neonatal outcomes of women with partial Dunnigan lipodystrophy.

Introduction: Lipodystrophies are a group of disorders characterized by selective and variable loss of adipose tissue, which can result in an increased risk of insulin resistance and its associated complications. Women with lipodystrophy often have a high frequency of polycystic ovary syndrome (PCOS) and may experience gynecological and obstetric complications. The objective of this study was to describe the gestational outcomes of patients with familial partial lipodystrophy type 2 (FPLD2) at a reference center with the aim of improving the understanding and management of pregnant women affected by this condition. Methods: This was a retrospective analysis of data obtained from questionnaires regarding past pregnancies and a review of medical records from the beginning of follow-up in outpatient clinics. Results: All women diagnosed with FPLD2 who had previously become pregnant were included in this study (n=8). The women in the study experienced pregnancies between the ages of 14 and 38 years, with an average of 1.75 children per woman. The pregnancies in question were either the result of successful conception within 12 months of attempting to conceive or unplanned pregnancies. During pregnancy, two women (25%) were diagnosed with gestational diabetes mellitus (GDM), one (12.5%) with gestational hypothyroidism, and one (12.5%) with preeclampsia. Among the 17 pregnancies, two miscarriages (11.8%) occurred, and five cases (29.4%) of macrosomia were observed. Four instances of premature birth and an equal number of neonatal hypoglycemia cases were recorded. The reported neonatal complications included an unspecified malformation, respiratory infection, and two neonatal deaths related to heart malformation and respiratory distress syndrome. Conclusion: Our data showed a high frequency of fetal complications in women with FPLD2. However, no instances of infertility or prolonged attempts to conceive have been reported, highlighting the significance of employing effective contraception strategies to plan pregnancies at optimal times for managing metabolic comorbidities.

2024 UPDATE: the Brazilian Diabetes Society position on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) in people with prediabetes or type 2 diabetes.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease affecting 30% of the world's population and is often associated with metabolic disorders such as metabolic syndrome, type 2 diabetes (T2D), and cardiovascular disease. This review is an update of the Brazilian Diabetes Society (Sociedade Brasileira de Diabetes [SBD]) evidence-based guideline for the management of MASLD in clinical practice. METHODS: The methodology was published previously and was defined by the internal institutional steering committee. The SBD Metabolic Syndrome and Prediabetes Department drafted the manuscript, selecting key clinical questions for a narrative review using MEDLINE via PubMed with the MeSH terms [diabetes] and [fatty liver]. The best available evidence was reviewed, including randomized clinical trials (RCTs), meta-analyses, and high-quality observational studies related to MASLD. RESULTS AND CONCLUSIONS: The SBD Metabolic Syndrome and Prediabetes Department formulated 9 recommendations for the management of MASLD in people with prediabetes or T2D. Screening for the risk of advanced fibrosis associated with MASLD is recommended in all adults with prediabetes or T2D. Lifestyle modification (LSM) focusing on a reduction in body weight of at least 5% is recommended as the first choice for these patients. In situations where LSMs are insufficient to achieve weight loss, the use of anti-obesity medications is recommended for those with a body mass index (BMI) ≥ 27 kg/m2. Pioglitazone and glucagon-like peptide-1 receptor agonists (GLP-1RA) monotherapy are the first-line pharmacological treatments for steatohepatitis in people with T2D, and sodium-glucose cotransporter-2 (SGLT2) inhibitors may be considered in this context. The combination of these agents may be considered in the treatment of steatohepatitis and/or fibrosis, and bariatric surgery should be considered in patients with a BMI ≥ 35 kg/m2, in which the combination of LSM and pharmacotherapy has not been shown to be effective in improving MASLD.

Waist circumference is independently associated with liver steatosis and fibrosis in LMNA-related and unrelated Familial Partial Lipodystrophy women.

BACKGROUND: Lipodystrophies are a heterogeneous group of diseases characterized by the selective loss of subcutaneous adipose tissue and ectopic fat deposition in different organs, including the liver. This study aimed to determine the frequencies of liver steatosis (LS) and liver fibrosis (LF) in a sample of individuals with LMNA-related and unrelated Familial Partial Lipodystrophy. METHODS: This cross-sectional study included 17 women with LMNA-related FPLD and 15 women with unrelated FPLD. LS and LF were assessed using transient elastography (TE) with FibroScan®. Anthropometric and biochemical variables were included in a multiple linear regression analysis to identify the variables that were independently related to liver disease. RESULTS: Regarding the presence of LF, 22 (68.2%) women were classified as having non-significant fibrosis, and 10 (31.8%) were classified as having significant or severe fibrosis. Regarding LS, only six women (20.7%) were classified as having an absence of steatosis, and 23 (79.3%) had mild to severe steatosis. After multiple linear regression, waist circumference (but not age, body mass index, or waist-to-hip ratio) was found to be independently related to LS and LF. Among the biochemical variables, only triglyceride levels were independently related to LS but not LF. CONCLUSIONS: In women with FPLD, visceral fat accumulation appears to be the most important determinant of liver disease, including LF, rather than fat scarcity in the lower limbs.

NAFLD as a continuum: from obesity to metabolic syndrome and diabetes.

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing rapidly. It is nowadays recognized as the most frequent liver disease, affecting a quarter of global population and regularly coexisting with metabolic disorders such as type 2 diabetes, hypertension, obesity, and cardiovascular disease. In a more simplistic view, NAFLD could be defined as an increase in liver fat content, in the absence of secondary cause of steatosis. In fact, the clinical onset of the disease is a much more complex process, closely related to insulin resistance, limited expandability and dysfunctionality of adipose tissue. A fatty liver is a main driver for a new recognized liver-pancreatic α-cell axis and increased glucagon, contributing to diabetes pathophysiology. MAIN TEXT: This review will focus on the clinical and pathophysiological connections between NAFLD, insulin resistance and type 2 diabetes. We reviewed non-invasive methods and several scoring systems for estimative of steatosis and fibrosis, proposing a multistep process for NAFLD evaluation. We will also discuss treatment options with a more comprehensive view, focusing on the current available therapies for obesity and/or type 2 diabetes that impact each stage of NAFLD. CONCLUSION: The proper understanding of NAFLD spectrum-as a continuum from obesity to metabolic syndrome and diabetes-may contribute to the early identification and for establishment of targeted treatment.

DPP4 activity is related to body weight and central fat in postmenopausal women.

AIMS: Dipeptidyl peptidase-4 (DPP4) is a new adipokine increased in central obesity and related to insulin resistance (IR). Postmenopausal (PM) state may be associated with increase in body weight and central fat distribution. We hypothesize that DPP4 is increased in PM women. MATERIALS AND METHODS: Twenty-two non-obese PM and 22 non-obese premenopausal women (PreM), were evaluated. DPP4 activity, lipid profile, HbA1c, FSH, estradiol and sex hormone-binding globulin (SHBG) were measured; an oral glucose tolerance test (OGTT) was performed and IR calculated. Body composition was assessed by dual X-ray absorptiometry (DXA). Correlations between DPP4 and the anthropometric and metabolic variables and body fat distribution were studied. RESULTS: DPP4 activity was not different between the two groups (PM 5309 ±â€¯650 vs PreM 5387 ±â€¯704 RLU; p = 0,70). In the PM group there was a significant correlation between DPP4 and body weight (r = 0,498; p = 0,03; n = 22) and trunk fat (r = 0,477; p = 0,03; n = 21). There was also a trend for correlation with android (r = 0,418; p = 0,06; n = 21) and total fat (r = 0,409; p = 0,06; n = 21). When stratified by BMI, DPP4 was significantly higher in PM women with BMI ≥25 kg/m2 (p = 0,02). CONCLUSION: DPP4 was not increased in PM but is associated with body weight and body fat centralization.

Pancreatic fat deposition is increased and related to beta-cell function in women with familial partial lipodystrophy.

BACKGROUND: To study pancreatic fat deposition and beta-cell function in familial partial lipodystrophy (FPLD) patients. METHODS: In a cross-sectional study, eleven patients with FPLD, and eight healthy volunteers were matched for age and body mass index and studied at a referral center. Body composition was assessed using dual-energy X-ray absorptiometry and the Dixon method of magnetic resonance imaging was used to quantify pancreatic and liver fat. Fasting plasma glucose, insulin, leptin, lipids and homeostasis model assessment of insulin resistance values were measured, and an oral glucose tolerance test was performed. The insulinogenic index, Matsuda insulin sensitivity index and beta-cell disposition index were calculated. RESULTS: The FPLD group presented a higher waist-to-hip ratio and fat mass ratio and lower total, truncal and lower-limb fat masses. Pancreatic and liver fat contents (log transformed) were significantly higher in the FPLD group (5.26 ± 1.5 vs. 4.08 ± 0.64, p = 0.034 and 0.77 ± 0.50 vs. 0.41 ± 0.18, p = 0.056, respectively). Pancreatic fat was inversely related to the DI (r = - 0.53, p = 0.027) and HDL-cholesterol (r = - 0.63, p = 0.003) and directly related to WHR (r = 0.60; p = 0.009), HbA1c (r = 0.58; p = 0.01) and serum triglyceride (r = 0.48, p = 0.034). Higher triglyceride and lower HDL-cholesterol levels were observed in the FPLD group. CONCLUSIONS: This study demonstrated for the first time that pancreatic fat deposition is increased in FPLD. Moreover, an inverse relationship was demonstrated between pancreatic fat and beta-cell function. The findings of this study may be consistent with the expandability hypothesis and the twin cycle hypothesis.

Is DPP4 activity increased in PCOS?

AIMS: Dipeptidyl peptidase-4 (DPP4) is an adipokine with greater expression in visceral fat and related with insulin resistance (IR). Polycystic ovary syndrome (PCOS) is also associated with IR. Our study aims to evaluate DPP4 activity in PCOS. MATERIALS AND METHODS: Thirty PCOS patients were compared to 28 healthy women. Body composition by dual X-ray absorptiometry (DXA), plasma activity of DPP4 and biochemical variables were performed. All participants underwent an oral glucose tolerance test for insulin and glucose analysis. RESULTS: DPP4 activity was similar in both groups (PCOS 5823 ±â€¯926 vs Control 5501.8 ±â€¯975; p = 0.20). PCOS patients were more IR with lower levels of SHBG (32 vs 47, p = 0.02) and Matsuda index (15.6 vs 20.4, p = 0.03) and higher HOMA-IR (2.8 vs 1.7, p < 0.01), in addition to increased levels of testosterone (55 vs 25, p < 0.01). DPP4 was correlated to HbA1c (r = 0.279, p = 0.03), HDL-c (r = -0.28, p = 0.03) and SHBG (r = -0.256, p = 0.05). CONCLUSIONS: Although PCOS was well characterized as IR and hyperandrogenic, DPP4 was not different in this group. However, a relationship between DPP4 and markers of IR were found. More studies are warranted.

A Novel Generalized Lipodystrophy-Associated Progeroid Syndrome Due to Recurrent Heterozygous LMNA p.T10I Mutation.

Background: Lamin A/C (LMNA) gene mutations cause a heterogeneous group of progeroid disorders, including Hutchinson-Gilford progeria syndrome, mandibuloacral dysplasia, and atypical progeroid syndrome (APS). Five of the 31 previously reported patients with APS harbored a recurrent de novo heterozygous LMNA p.T10I mutation. All five had generalized lipodystrophy, as well as similar metabolic and clinical features, suggesting a distinct progeroid syndrome. Methods: We report nine new patients and follow-up of two previously reported patients with the heterozygous LMNA p.T10I mutation and compare their clinical and metabolic features with other patients with APS. Results: Compared with other patients with APS, those with the heterozygous LMNA p.T10I mutation were younger in age but had increased prevalence of generalized lipodystrophy, diabetes mellitus, acanthosis nigricans, hypertriglyceridemia, and hepatomegaly, together with higher fasting serum insulin and triglyceride levels and lower serum leptin and high-density lipoprotein cholesterol levels. Prominent clinical features included mottled skin pigmentation, joint contractures, and cardiomyopathy resulting in cardiac transplants in three patients at ages 13, 33, and 47 years. Seven patients received metreleptin therapy for 0.5 to 16 years with all, except one noncompliant patient, showing marked improvement in metabolic complications. Conclusions: Patients with the heterozygous LMNA p.T10I mutation have distinct clinical features and significantly worse metabolic complications compared with other patients with APS as well as patients with Hutchinson-Gilford progeria syndrome. We propose that they be recognized as having generalized lipodystrophy-associated progeroid syndrome. Patients with generalized lipodystrophy-associated progeroid syndrome should undergo careful multisystem assessment at onset and yearly metabolic and cardiac evaluation, as hyperglycemia, hypertriglyceridemia, hepatic steatosis, and cardiomyopathy are the major contributors to morbidity and mortality.

Dipeptidyl peptidase-4 levels are increased and partially related to body fat distribution in patients with familial partial lipodystrophy type 2.

BACKGROUND: Dipeptidyl peptidase-4 (DDP4) is an enzyme responsible for glucagon-like peptide-1 inactivation and plays an important role in glucose metabolism. OBJECTIVE: The aim of this study was to evaluate DPP4 levels in patients with familial partial lipodystrophy type 2 (FPLD2) and correlate it with body fat distribution. METHODS: Fourteen patients with FPLD2 were selected to participate in this study and matched to a healthy control group (n = 8). All participants had anthropometrical data registered. Body adiposity index (BAI) was used to evaluate fat distribution in this population. Body fat content and distribution were analyzed by dual X-ray absorptiometry (DXA). Biochemical exams, including DPP4 levels, were performed in all individuals. RESULTS: Despite the same body mass index, lipodystrophic patients had a significant lower hip (median 92.0 vs 94.5; p = 0.028), HDL cholesterol (42.6 ± 10.4 vs 66.1 ± 16.0; p < 0.01) and BAI (24.1 ± 2.8 vs 29.0 ± 3.7; p = 0.02), suggesting that BAI was able to catch differences in fat distribution between groups. On the other hand, patients with FPLD2 presented significant higher levels of insulin (median 11.2 vs 5.3; p = 0.015), triglycerides (184.9 ± 75.4 vs 89.1 ± 51.0; p < 0.01) and DPP4 (4.89 ± 0.92 vs 3.93 ± 1.08; p = 0.04). A trend toward an inverse statistical significance was observed between DPP4 levels and BAI (r = -0.38; p = 0.072). In the lipodistrophic group, a significant correlation was found between DPP4 levels and percentage of total body fat (r = 0.86; p = 0.0025) and android fat (r = 0.78; p = 0.014). CONCLUSIONS: Patients with FPLD2 exhibit an increase in DDP4 levels in comparison to a healthy control group. The increase in the levels of this enzyme does not seem to be related to the diagnosis of diabetes and might be associated with an increase in central fat (estimated using BAI and measured using DXA). These results might be used to reinforce the concept that DDP4 is an adipokine related to central fat distribution.

Impact of a 6-month treatment with intragastric balloon on body composition and psychopathological profile in obese individuals with metabolic syndrome.

BACKGROUND: The aim of this study was to investigate the effects of a 6-month treatment with intragastric balloon (IGB) on body composition and depressive/anxiety symptoms in obese individuals with metabolic syndrome (MS). METHODS: Fifty patients (aged 18-50 years) with obesity and MS were selected for treatment with IGB for 6 months. Body composition was verified with dual-energy X-ray absorptiometry (DXA) at baseline and right after IGB removal. Anxiety/depressive symptoms were assessed with the Beck Depression Inventory (BDI) and the hospital anxiety and depression scale (HADS) at baseline and after 6 months of treatment. RESULTS: In total, 39 patients completed the study. After 6 months, there were significant decreases in weight (11.7 ± 9.6 kg, p < 0.0001) and waist circumference (9.3 ± 8.2 cm, p < 0.0001). Weight loss was also demonstrated by DXA and corresponded to decreases of 3.0 ± 3.4% in body fat percentage, 7.53 ± 7.62 kg in total body fat, and 3.70 ± 4.89 kg in lean body mass (p < 0.001 for all comparisons). Depressive symptoms scores decreased by a mean of 4.57 ± 10.6 points when assessed with the BDI (p = 0.002) and 1.82 ± 5.16 points when assessed with the HADS-Depression (p = 0.0345). Anxiety symptoms scores decreased by a mean of 1.84 ± 4.04 points when determined with the HADS-anxiety (p = 0.0066). The decrease in body fat percentage was the parameter that best correlated with improvements in depressive (p = 0.008) and anxiety symptoms (p = 0.014). CONCLUSIONS: In obese individuals with MS, fat mass reduction was associated with short-term improvements in depressive and anxiety symptoms. Trial Registration Registered at ClinicalTrials.gov, NCT01598233.

Erratum: Body composition study by dual-energy x-ray absorptiometry in familial partial lipodystrophy: finding new tools for an objective evaluation.

[This corrects the article DOI: 10.1186/1758-5996-4-40.].

The role of glucagon on type 2 diabetes at a glance.

The opposite effects of insulin and glucagon in fuel homeostasis, the paracrine/endocrine inhibitory effects of insulin on glucagon secretion and the hyperglucagonemia in the pathogenesis of type 2 diabetes (T2D) have long been recognized. Inappropriately increased alpha-cell function importantly contributes to hyperglycemia and reflects the loss of tonic restraint normally exerted by high local concentrations of insulin on alpha-cells, possibly as a result of beta-cell failure and alpha-cell insulin resistance, but additional mechanisms, such as the participation of incretin hormones in this response, have also been suggested. Three classes of drugs already available for clinical use address the abnormalities of glucagon secretion in T2D, namely, the GLP-1 receptor agonists (GLP-1RA), the inhibitors of dipeptidyl peptidase-4 (DPP-4i) and the amylin agonist pramlintide; it has been proposed that the glucagonostatic and insulinotropic effects of GLP-1RA equally contribute to their hypoglycemic efficacy. In this review, the control of glucagon secretion and its participation in T2D pathogenesis are summarized.

Body composition and depressive/anxiety symptoms in overweight and obese individuals with metabolic syndrome.

BACKGROUND: Several studies point to a correlation between obesity and the severity of depressive and anxiety symptoms in children and adults, but there are still some controversial points about this association. The aim of this study is to investigate the relationship between body composition and the severity of anxiety/depressive symptoms in overweight and obese individuals with Metabolic Syndrome (MS). METHODS: Fifty patients, 18-50 years old, overweight or obese and with the diagnosis of MS based on the International Diabetes Federation (IDF) criteria were selected for this study. Body composition was evaluated using Dual Energy X-ray Absorptiometry (DXA). Depressive symptoms were evaluated using the Hospital Anxiety and Depression Scale (HADS-Depression) and the Beck Depression Inventory (BDI). Anxiety symptoms were evaluated using HADS-Anxiety. RESULTS: No correlation was found between depressive symptoms (HADS-Depression or BDI) and Body Mass Index (BMI) (r = 0.01; p = 0.94 and r = -0.12, p = 0.38; respectively), Waist Circumference (WC) (r = -0.06, p = 0.67 and r = -0.22, p = 0.12; respectively), and Waist-to-Hip Ratio (WHR) (r = -0.12, p = 0.40 and r = -0.17, p = 0.23; respectively). Additionally, no correlation was found among anxiety symptoms (HADS-Anxiety) and BMI (r = -0.15, p = 0.27), and WHR (r = -0.17, p = 0.24). In contrast, a significant correlation was found between percentage of total fat (DXA) and HADS-Depression (r = 0.34, p = 0.019) and HADS-Anxiety (r = 0.30, p = 0.039). Additionally, an inverse and strong correlation was found between lean mass (in grams) and HADS-Depression (r = -0.42, p = 0.004), HADS anxiety (r = -0.57, p < 0.0001), and BDI (r = -0.44, p = 0.026). CONCLUSIONS: In individuals with MS, the percentage of body fat, and not central fat, BMI, WC, or WHR, was associated with an increased severity of anxiety and depressive symptoms. In contrast, total lean mass was strongly associated with fewer anxiety/depressive symptoms, suggesting that body composition might be related to psychiatric comorbidity in overweight individuals with MS.

Body composition study by dual-energy x-ray absorptiometry in familial partial lipodystrophy: finding new tools for an objective evaluation.

BACKGROUND: Familial partial lipodystrophies (FPLD) are clinically heterogeneous disorders characterized by selective loss of adipose tissue, insulin resistance and metabolic complications. Until genetic studies become available for clinical practice, clinical suspicion and pattern of fat loss are the only parameters leading clinicians to consider the diagnosis. The objective of this study was to compare body composition by dual energy X-ray absorptiometry (DXA) in patients with FPLD and control subjects, aiming to find objective variables for evaluation of FPLD. METHODS: Eighteen female patients with partial lipodystrophy phenotype and 16 healthy controls, matched for body mass index, sex and age were studied. All participants had body fat distribution evaluated by DXA measures. Fasting blood samples were obtained for evaluation of plasma leptin, lipid profile and inflammatory markers. Genetic studies were carried out on the 18 patients selected that were included for statistical analysis. Thirteen women confirmed diagnosis of Dunnigan-type FPLD (FPLD2). RESULTS: DXA revealed a marked decrease in truncal fat and 3 folds decrease in limbs fat percentage in FPLD2 patients (p <0.001). Comparative analysis showed that ratio between trunk and lower limbs fat mass, characterized as Fat Mass Ratio (FMR), had a greater value in FLPD2 group (1.86 ± 0.43 vs controls 0.93 ± 0.10; p <0.001) and a improved accuracy for evaluating FPLD2 with a cut-off point of 1.2. Furthermore, affected women showed hypoleptinemia (FLPD2 4.9 ± 2.0 vs controls 18.2 ± 6.8; p <0.001), insulin resistance and a more aggressive lipid profile. CONCLUSION: In this study, assessment of body fat distribution by DXA permitted an objective characterization of FLPD2. A consistent pattern with marked fat reduction of lower body was observed in affected patients. To our knowledge this is the first time that cut-off values of objective variables were proposed for evaluation of FPLD2.

Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations.

OBJECTIVE: Mutations in LMNA have been linked to diverse disorders called laminopathies, which display heterogeneous phenotypes and include diseases affecting muscles, axonal neurons, progeroid syndromes, and lipodystrophies. Among the lipodystrophies, LMNA mutations have been reported most frequently in patients with familial partial lipodystrophy (FPLD) of the Dunnigan variety; however, phenotypic heterogeneity in the pattern of body fat loss has been observed. In this study, we searched for LMNA mutations in patients with various forms of lipodystrophy. DESIGN AND METHODS: We studied 21 unrelated individuals with lipodystrophy. Subjects underwent a complete clinical evaluation and were classified as typical FPLD (n=12), atypical partial lipodystrophy (n=7), or generalized lipodystrophy (n=2). Molecular analysis of LMNA gene, analysis of body fat by dual-energy X-ray absorptiometry, and biochemical measurements were performed. RESULTS: ALL PATIENTS WITH TYPICAL FPLD WERE FOUND TO CARRY LMNA MUTATIONS: seven patients harbored the heterozygous p.R482W (c.1444C>T), two patients harbored the p.R482Q (c.1445G>A), and two individuals harbored the novel heterozygous variant p.N466D (c.1396A>G), all in exon 8. Also, a homozygous p.R584H (c.1751 G>A) mutation in exon 11 was found. Among patients with atypical partial lipodystrophy, two of them were found to have LMNA mutations: a novel heterozygous p.R582C variation (c.1744 C>T) in exon 11 and a heterozygous substitution p.R349W (c.1045C>T) in exon 6. Among patients with generalized lipodystrophy, only one harbored LMNA mutation, a heterozygous p.T10I (c.29C>T) in exon 1. CONCLUSIONS: We have identified LMNA mutations in phenotypically diverse lipodystrophies. Also, our study broadens the spectrum of LMNA mutations in lipodystrophy.

A new method for body fat evaluation, body adiposity index, is useful in women with familial partial lipodystrophy.

BMI is a widely used method to evaluate adiposity. However, it has several limitations, particularly an inability to differentiate lean from fat mass. A new method, body adiposity index (BAI), has been recently proposed as a new measurement capable to determine fat excess better than BMI. The aim of this study was to investigate BAI as a mean to evaluate adiposity in a group of women with familial partial lipodystrophy (FPLD) and compare it with BMI. Thirteen women with FLPD Dunnigan type (FPLD2) and 13 healthy volunteers matched by age and BMI were studied. Body fat content and distribution were analyzed by dual X-ray absorptiometry (DXA). Plasma leptin was also measured. BAI was significantly lower in FPLD2 in comparison to control group (24.6 ± 1.5 vs. 30.4 ± 4.3; P < 0.001) and presented a more significant correlation with total fat (%) (r = 0.71; P < 0.001) and fat Mass (g) (r = 0.80; P < 0.001) than BMI (r = 0.27; P = 0.17 for total fat and r = 0.52; P = 0.006 for fat mass). There was a correlation between leptin and BAI (r = 0.57; P = 0.01), [corrected] but not between leptin and BMI. In conclusion, BAI was able to catch differences in adiposity in a sample of FPLD2 patients. It also correlated better with leptin levels than BMI. Therefore, we provide further evidence that BAI may become a more reliable indicator of fat mass content than the currently available measurements.

Serum retinol binding protein 4 is not decreased in congenital generalized lipodystrophy: a case series.

INTRODUCTION: Previous studies have suggested that Retinol Binding Protein 4 (RPB4), a protein produced by the adipose tissue, is associated with insulin resistance (IR). Congenital Generalized Lipodystrophy (CGL) is a rare disease characterized by IR and paucity of adipose tissue. Our objective was to determine RBP4 levels in patients with CGL. SUBJECTS AND METHODS: Six (6) patients with CGL and a healthy control group were selected to participate in the study. Anthropometric and biochemical variables were compared between groups. RESULTS: No difference was observed in RBP4 levels between the two groups (CGL 42.5 [12.5 - 127] vs. control 57.4 [15.9 - 165]; p = 0.78). On the other hand, leptin levels were significantly lower in CGL patients (CGL 0.65 [0.2 - 0.7] vs. control 10.9 [0.9 - 38.6]; p = 0.015). No correlation was found between RBP-4 and waist circunference (r = 0.18, p = 0.57), or BMI (r = 0.24, p = 0.45). CONCLUSION: RBP4 is not decreased in CGL. These results suggest that adipose tissue may not be the main source of RBP4.

Serum retinol binding protein 4 is not decreased in congenital generalized lipodystrophy: a case series / Os níveis plasmáticos da retinol binding protein 4 (rbP4) não estão reduzidos na lipodistrofia congênita generalizada: uma série de casos

INTRODUCTION: Previous studies have suggested that Retinol Binding Protein 4 (RPB4), a protein produced by the adipose tissue, is associated with insulin resistance (IR). Congenital Generalized Lipodystrophy (CGL) is a rare disease characterized by IR and paucity of adipose tissue. Our objective was to determine RBP4 levels in patients with CGL. SUBJECTS AND METHODS: Six (6) patients with CGL and a healthy control group were selected to participate in the study. Anthropometric and biochemical variables were compared between groups. RESULTS: No difference was observed in RBP4 levels between the two groups (CGL 42.5 [12.5 - 127] vs. control 57.4 [15.9 - 165]; p = 0.78). On the other hand, leptin levels were significantly lower in CGL patients (CGL 0.65 [0.2 - 0.7] vs. control 10.9 [0.9 - 38.6]; p = 0.015). No correlation was found between RBP-4 and waist circunference (r = 0.18, p = 0.57), or BMI (r = 0.24, p = 0.45). CONCLUSION: RBP4 is not decreased in CGL. These results suggest that adipose tissue may not be the main source of RBP4.

INTRODUÇÃO: Estudos prévios sugeriram que os níveis plasmáticos da retinol binding protein (RBP4), uma proteína do tecido adiposo, estão associados com a resistência à insulina (RI). A lipodistrofia congênita generalizada (LCG) é uma doença rara caracterizada por ausência de tecido adiposo e RI. O objetivo é determinar os níveis de RBP4 em pacientes com LCG. SUJEITOS E MÉTODOS: Seis (6) pacientes com LCG e um grupo controle saudável foram selecionados para participar no estudo. As variáveis antropométricas e bioquímicas foram comparadas quando comparados os grupos. RESULTADOS: Nenhuma diferença foi observada entre os níveis de RBP4 log entre os grupos (LCG 42,5 [12,5 - 127] vs. controle 57,4 [15,9 - 165]; p = 0,78). Por outro lado, os níveis de leptina foram menores em pacientes com LCG (LCG 0,65 [0,2 - 0,7] vs. controle 10.9 [0,9 - 38,6]; p = 0,015). Nenhuma correlação foi encontrada entre RBP4 e cintura (r = 0,18, p = 0,57) ou IMC (r = 0,24, p = 0,45). CONCLUSÃO: RBP4 não está diminuída na LCG. Esses resultados sugerem que o tecido adiposo pode não ser a principal fonte de RBP4.

Insulin resistance in obesity and metabolic syndrome: is there a connection with platelet l-arginine transport?

OBJECTIVE: Nitric oxide (NO) is a short-lived gaseous messenger with multiple physiological functions including regulation of blood flow, platelet adhesion and aggregation inhibition. NO synthases (NOS) catalyze the conversion of cationic amino acid L-arginine in L-citrulline and NO. Despite an increasing prevalence of obesity and metabolic syndrome (MetS) in the last decades, the exact mechanisms involved in the pathogenesis and cardiovascular complications are not fully understood. We have examined the effects of obesity and MetS on the L-arginine-NO-cGMP pathway in platelets from a population of adolescents. MATERIALS: A total of twenty six adolescent patients (13 with obesity and 13 with MetS) and healthy volunteers (n=14) participated in this study. Transport of L-arginine, NO synthase (NOS) activity and cGMP content in platelets were analyzed. Moreover, platelet function, plasma levels of L-arginine, metabolic and clinical markers were investigated in these patients and controls. RESULTS: L-arginine transport (pmol/10(9) cells/min) in platelets via system y(+)L was diminished in obese subjects (20.8±4.7, n=10) and MetS patients (18.4±3.8, n=10) compared to controls (52.3±14.8, n=10). The y(+)L transport system correlated negatively to insulin levels and Homeostasis Model Assessment of Insulin Resistance (HOMA IR) index. No differences in NOS activity and cGMP content were found among the groups. Moreover, plasma levels of L-arginine were not affected by obesity or MetS. DISCUSSION: Our study provides the first evidence that obesity and MetS lead to a dysfunction of L-arginine influx, which negatively correlates to insulin resistance. These findings could be a premature marker of future cardiovascular complications during adulthood.